The application of a direct current (DC) electric field to generate charged liquid droplets from Taylor cones in DC electrospray is widely used in pharmaceutical mass spectrometry because of its ability to produce a beam of relatively mono-dispersed and small (e.g., <100 nm) charged droplets that can contain individual protein molecules, see J. B. Fenn, M. Mann, C. K. Meng, S. F. Wong, and C. M. Whitehouse, Science 246, 64, 1989, the entire contents and disclosure of which is hereby incorporated by reference. Other areas of application include electrostatic printing, nano-particle technology, micro-encapsulation, fiber electrospinning, etc., see G. Castano, and V. Hruby, J. Fluid Mech. 459, 245, 2001, G. Loscertales, A. Barrero, I. Guerrero, R. Cortijo, M. Marquez, and A. M. Ganan-Calvo, Science 295, 1695, 2002, the entire contents and disclosures of which are hereby incorporated by reference. The DC field and interfacial charges combine to produce a Maxwell force that stretches the drop into a conic shape (known as a Taylor cone) and ejects streams of small charged droplets from the tip at large frequencies (>1 kHz).
The Taylor cone is formed due to a static balance between the azimuthal capillary stress and the Maxwell normal stress exerted by the predominantly tangential and singular electric field in the liquid. For electrolyte spraying from a DC Taylor cone, surface ions from the bulk electrolyte are transported and concentrated at the tip to drive a Rayleigh fission process. Spraying of dielectric liquid via DC Taylor cones is also possible, but it requires significantly higher voltages and is believed to be driven by the momentum and mass flux of an ion evaporation process at the cone tip, see M. Gamero-Castano and J. Fernandez de Ia Mora, J. of Mass Spectrom., 35, 790-803, 2000, the entire contents and disclosure of which is hereby incorporated by reference.
In DC electrospraying, a steady, continuous beam of sub-micron charged droplets (typically 0.2-0.3 microns) stream out in a Taylor cone. A typical image of a DC Taylor cone obtained by spraying ethanol into air using DC electric fields is shown in FIG. 1. The Taylor cone and the spray initiation for ethanol depends on several experimental conditions, but is typically observed beyond 2-3 kilovolts.
There has been little investigation into using an AC field for an electrospray. In earlier AC electrospray work it was expected that, at high frequency, the net Maxwell stress would vanish and drop ejection would be impossible. The few reported studies concentrated on low frequencies and superimposing a small AC bias onto a large DC field, see S. B. Sample, and R. Bollini, J. Colloid Interface Sci., 41, 185, 1972; and M. Sato. J. Electrostatics, 15, 237, 1984, the entire contents and disclosures of which are hereby incorporated by reference.
Both of the studies described above, however, do not report spraying dynamics that are fundamentally different from a DC electrospray. One other reported work consisted of using a high frequency AC electric field with 30 kHz and 45 kHz frequencies, see G. Gneist and H. J. Bart, Chem. Eng. Technol., 25, 129-133, 2002, the entire contents and disclosure of which is hereby incorporated by reference. However, this work involved dispersing drops into an ambient liquid medium purely with the intention of generating emulsion drops in liquid/liquid systems.
Mass spectrometry is a common chemical analysis technique used in fields such as environmental analysis, forensic chemistry, health care, and the like. Detection and identification of biomolecules such as DNA, peptides, proteins, and other molecular biomarkers, form the core of a biotechnology industry, and mass spectrometry plays a significant role in developing this sector. However, use of mass spectrometry in both research and practical fields is often limited by the ionization source, which either does not produce a sufficient number of sample ions for detection, fragments the sample ions limiting detection capability, or does not efficiently transfer the ions into the mass spectrometer.
Proteomics, the large-scale study of proteins, benefited from the disclosure of a direct current electrospray ionization (DC ESI) in the 1980s, as DC ESI is a soft ionization technique that does not fragment the charged molecules during analysis. Another soft ionization technique is Matrix Assisted Laser Desorption Ionization (MALDI) that was identified around the same time as DC ESI. Together, DC ESI and MALDI helped foster mass spectrometry as an analytical tool for the study of several classes of biomolecules.
DC ESI, however, relies on the formation of a sharp conical meniscus called a Taylor cone, by the application of a high DC voltage across a liquid source. The charged droplets that are generated from the tip of the Taylor cone undergo successive Rayleigh fission to ultimately yield a quasi-molecular ion that can be detected by mass spectrometry. One feature of DC ESI is that it can generate multiple charged states, depending upon the size of the molecule. Thus, mass spectrometers with limited mass-to-charge ratio (m/z) detection capability can be used to detect molecules with high molecular mass, such as proteins. In negative mode DC ESI (e.g. to generate anions), however, an electron discharge can form that interferes with the mass spectra and yields a mass spectrum with a low signal-to-noise (S/N) ratio, indicative of a poor sensitivity and a limit on mass spectrometer performance. Thus, the phenomenon of electron discharge limits the use of DC ESI extensively to positive mode mass spectrometry.
Unlike DC ESI that utilizes electrical energy to generate ions from a liquid sample, MALDI uses light energy (e.g., a laser beam) to generate ions from a solid sample. Although MALDI generates only monovalent or sometimes, bivalent charge states of biomolecules, MALDI is typically utilized for negative mode mass spectrometry due to the disadvantages associated with DC ESI.
There is, therefore, a need for an improved mass spectra analysis. Because high frequency AC only entrains low mobility charged species, the high mobility electrons are substantially always in equilibrium and not discharged. AC ESI, therefore, yields a better signal-to-noise ratio in the mass spectra, even in negative mode. The mechanism of the examples described herein offers a preferential entrainment of ions and further pre-concentrates the analyte ions in the liquid cone and improves the signal intensity, in some instances, buy an order of magnitude. As such, AC ESI combines the benefits of both MALDI and DC ESI.